Arachidonic acid derivatives synthesized by vascular and nonvascular compartments of the kidney contribute to the regulation of blood flow, vascular tone and platelet aggregability. Over the past years, a large number of studies were devoted to the traditional primary prostaglandins, PGE2 and PGF2 alpha, and various physiological and pathological roles have been ascribed to them. Two recent discoveries, first that the same tissues that synthesize primary prostaglandins have also the capacity to produce TxA2 and PGI2 and second that the capacity of renal cortex to synthesize prostaglandin is under control of an endogenous protaglandin synthetase inhibitor still uncharacterized, calls for re-evaluation of earlier data. In this proposal, we intend to investigate what are the factors controlling prostaglandin release and how prostaglandins operating within the kidney contribute to homeostatic mechanisms. To define this contribution, we will study the interaction of locally generated arachidonic acid derivative with vasoactive hormones in the dog kidney, using in vivo and in vitro preparations. We will investigate the factors that influence the release of prostaglandins or thromboxane from the kidney and the change in species of arachidonic acid metabolites produced as affected by endogenous activation or inhibition of the renin-angiotensin, kallikrein-kinin and autonomic nervous systems. Alterations in the metabolism of prostaglandins will be related to hemodynamic changes occurring in vivo. Prostaglandin metabolizing enzymes are going to be studied in the same tissues in an attempt to obtain a clearer understanding of how prostaglandin mechanisms operating within the kidney contribute to the regulation of renal hemodynamics.